My career goals are focused upon two concurrent diseases, childhood obesity and type 2 diabetes mellitus, affecting prominently adolescents of minority groups. Identifying new etiopathogenic mechanisms that explain the racial disparity and the potential influence of racial and lifestyle factors on predicting treatment outcomes are my long-term goals. With this focus, I am committed to patient-oriented translational research but I need to acquire specific skills that allow me to be more effective in this area. This award will allow me to accomplish these goals in the following way. I will: 1) enhance my statistical and epidemiological foundation; 2) develop skills in methodology, measurements, and analysis of epidemiological data; 3) develop the necessary knowledge in preventive medicine, pharmacoepidemiology and bioinformatics necessary for implementing interventional studies based on the experience gained in my training and the preliminary results of the proposed project. In obese African-American (AA) subjects, we have proposed that increased GLP-1 levels [marker of enteroinsular axis activity (EIA)] could promote adipogenesis and the development of comorbidities. It is still unclear whether these racial differences in EIA are determined by age, severity of overweight, differences in cardiorespiratory fitness (CRF) or autonomic nervous system (ANS) modulation. We will assess these three interrelated areas (EIA, CRF, and ANS modulation) in a biracial sample of wide-ranging overweight adolescents. In particular, we are interested in the relation between EIA activity and insulin dynamics as a potential mechanistic pathway to explain the increased prevalence of obesity, type 2 Diabetes Mellitus (T2DM) and Cardiovascular Disease (CVD) in AA youth. Therefore, we will determine the associations among EIA, CRF, glucose homeostasis, and risk factors for ICVD in adolescents. The results of this study can be translated into medical practice changes and may help to implement a more physiologically effective approach to obesity treatment in AA adolescents, in particular.